Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Feldmann, Marc; Maini, R. N.

doi:10.4049/jimmunol.1090051

Cited by 93 publications

(59 citation statements)

References 35 publications

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“…Anti-TNF antibody was the first cytokine-selective therapy that was shown to offer clear benefits in the setting of common disease in rheumatoid arthritis, being both effective and acceptably safe (44). Based upon our data, prophylaxis with anti-TNF antibody is a feasible therapeutic option that is ready to be exploited in the elective surgical setting.…”

Section: Discussionmentioning

confidence: 82%

Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline

Terrando

Monaco

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Cognitive decline following surgery in older individuals is a major clinical problem of uncertain mechanism; a similar cognitive decline also follows severe infection, chemotherapy, or trauma and is currently without effective therapy. A variety of mechanisms have been proposed, and exploring the role of inflammation, we recently reported the role of IL-1β in the hippocampus after surgery in mice with postoperative cognitive dysfunction. Here, we show that TNF-α is upstream of IL-1 and provokes its production in the brain. Peripheral blockade of TNF-α is able to limit the release of IL-1 and prevent neuroinflammation and cognitive decline in a mouse model of surgery-induced cognitive decline. TNF-α appears to synergize with MyD88, the IL-1/TLR superfamily common signaling pathway, to sustain postoperative cognitive decline. Taken together, our results suggest a unique therapeutic potential for preemptive treatment with anti-TNF antibody to prevent surgery-induced cognitive decline.innate immunity | surgical complications | delirium | dementia

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Section: Discussionmentioning

confidence: 82%

Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline

Terrando

Monaco

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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623

522

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“…In this respect, TNF-a is a central mediator of multiple aspects of synovial inflammation that can activate fibroblasts, osteoclasts, B, and T cells and is an established therapeutic target in JIA (23). IFN-g may also play a pathogenic role by activating macrophages, whereas IL-17 increases vascularization and induces influx of neutrophils to drive inflammation (24,25).…”

Section: Discussionmentioning

confidence: 99%

Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Bendersky

Marcu-Malina

Berkun

et al. 2012

The Journal of Immunology

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The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of γδ T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, Vγ9+Vδ2+ (Vγ9+) T cells, in JIA. We found that as opposed to CD4+ T cells, equally high percentages (∼35%) of Vγ9+ T cells in SF and peripheral blood (PB) produced TNF-α and IFN-γ. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for Vγ9Jγ1.2+ T cells, similarly amplified cytokine secretion by SF and PB Vγ9+ T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF > PB Vγ9+ T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although Vγ9+ T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4+CD25+FOXP3+ cells (regulatory T cells). Furthermore, coculture with the Vγ9+ T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial Vγ9+ T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation.

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“…However, these observations regarding the kinetics of clinical translation have held equally valid for other therapeutic approaches that have been investigated in multiple animal models of autoimmunity. For example, while TNFα blockade in rheumatoid arthritis and IBD [112], and α4β1 integrin blockade in MS [113], reached clinical practice relatively soon after initial investigations in relevant animal models, clinical translation of anti-CD3 therapy in T1D has proven to be a longer and more challenging path. However, the sluggish translation of findings from the NOD mouse to clinical practice does not necessarily constitute a comment on the clinical relevance of findings in this model so much as a testament to the unique challenges of developing novel therapies for T1D.…”

Section: Discussionmentioning

confidence: 99%

Helminth Infection and Type 1 Diabetes

Zaccone¹,

Hall²

2012

Rev Diabet Stud

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■ AbstractThe increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our coevolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.

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Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Cited by 93 publications

References 35 publications

Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline

Tumor necrosis factor-α triggers a cytokine cascade yielding postoperative cognitive decline

Cellular Interactions of Synovial Fluid γδ T Cells in Juvenile Idiopathic Arthritis

Helminth Infection and Type 1 Diabetes

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